The role of the AMPK/NLRP3 axis in osteoarthritic bone marrow lesions of the knee: from molecular mechanisms to clinical applications.

Knee osteoarthritis (KOA) is a major disabling disease worldwide, and the available treatments are largely limited to symptom control. The pathogenesis of bone marrow lesions (BMLs), a central driver of pain and progression, has not been fully elucidated. This review summarizes the core role of the AMP-activated protein kinase‒NOD-like receptor pyrin domain-containing protein 3 (AMPK‒NLRP3) signaling axis in BML pathogenesis and proposed a novel pathophysiological framework integrating metabolic dysfunction and the inflammatory response. Systematic literature analysis indicates that reduced AMPK activity may lead to overactivation of NLRP3 inflammasomes, forming a vicious cycle that promotes bone marrow lesion (BML) development. Based on these insights, we discusses potential therapeutic targets including AMPK activators, NLRP3 inhibitors, and autophagy enhancers, and proposes biomarker-based individualized therapeutic strategies. This review systematically elucidate the role of the AMPK/NLRP3 axis in KOA-related BMLs, integrats basic research and clinical observations, and provide a theoretical basis for novel therapeutic strategy development.